# Clinical Cases: Nervous Tissue - Neurons ## Case 1: Alzheimer Disease ### Clinical Image ![Alzheimer Disease - Neurofibrillary Tangles](case_01_image.jpg) *Source: [Wikipedia - Neurofibrillary Tangle](https://en.wikipedia.org/wiki/Neurofibrillary_tangle) - CC BY-SA 3.0* ### Case Presentation A 72-year-old retired professor is brought by his wife who reports progressive memory problems over 3 years. He forgets recent conversations, repeats questions, and recently got lost driving to a familiar location. He has also become withdrawn and apathetic. Neurological examination reveals impaired short-term memory with inability to recall 3 words after 5 minutes, difficulty with serial 7s and clock drawing, but intact motor and sensory function. MRI brain shows hippocampal atrophy and enlarged lateral ventricles. CSF analysis reveals decreased amyloid-beta-42 and elevated phosphorylated tau protein. He is diagnosed with probable Alzheimer disease. The neuropathological hallmarks (demonstrated in autopsy studies) are senile plaques (extracellular deposits of amyloid-beta peptide) and neurofibrillary tangles (intracellular aggregates of hyperphosphorylated tau protein). Neurofibrillary tangles appear as flame-shaped intraneuronal inclusions composed of paired helical filaments of abnormally phosphorylated tau. The tau protein normally stabilizes microtubules; when hyperphosphorylated, it detaches and aggregates, disrupting axonal transport. He is started on cholinesterase inhibitors for symptomatic treatment. ### Key Learning Points - Tau protein normally stabilizes microtubules essential for axonal transport - In Alzheimer disease, tau becomes hyperphosphorylated, detaches from microtubules, and aggregates into neurofibrillary tangles - Disruption of axonal transport (which requires intact microtubules) leads to synaptic dysfunction and neuronal death - Tangles appear as "flame-shaped" in pyramidal neurons (like those in hippocampus) or "globose" in other neuronal types - The degree of cognitive impairment correlates with neurofibrillary tangle burden and distribution (Braak staging) --- ## Case 2: Rabies Encephalitis ### Clinical Image ![Rabies - Negri Bodies](case_02_image.jpg) *Source: [Wikipedia - Rabies](https://en.wikipedia.org/wiki/Rabies) - CC BY-SA 3.0* ### Case Presentation A 35-year-old man presents with agitation, confusion, and hydrophobia (fear of water with violent spasms when attempting to drink) three weeks after being bitten by a stray dog while traveling in Southeast Asia. He did not receive post-exposure prophylaxis. He develops hypersalivation, aerophobia (fear of air drafts), and fluctuating consciousness. Physical examination reveals autonomic instability with alternating periods of agitation and calm. The clinical presentation is classic for furious (encephalitic) rabies. Despite intensive care, he deteriorates and dies within one week. Autopsy reveals lymphocytic encephalitis affecting the brainstem and limbic system. Histologically, neurons contain pathognomonic Negri bodies - eosinophilic, round to oval cytoplasmic inclusions representing sites of viral replication, most prominent in hippocampal pyramidal neurons and cerebellar Purkinje cells. The pathophysiology involves rabies virus entering neurons at the bite site and traveling via retrograde axonal transport to reach the CNS. ### Key Learning Points - Rabies virus exploits retrograde axonal transport (dynein-mediated movement along microtubules) to travel from peripheral nerve endings to neuronal cell bodies - The incubation period reflects the distance the virus must travel; bites closer to the CNS have shorter incubation - Negri bodies are eosinophilic intracytoplasmic inclusions found in infected neurons, pathognomonic for rabies - Neurons in the hippocampus (pyramidal cells) and cerebellum (Purkinje cells) are particularly affected - Understanding axonal transport explains how peripheral infection reaches the CNS and why post-exposure prophylaxis must be given before virus reaches the CNS --- ## Case 3: Peripheral Nerve Injury with Chromatolysis ### Clinical Image ![Chromatolysis - Neuronal Response to Injury](case_03_image.jpg) *Source: [Wikipedia - Chromatolysis](https://en.wikipedia.org/wiki/Chromatolysis) - CC BY-SA 4.0* ### Case Presentation A 28-year-old construction worker sustains a deep laceration to his forearm, severing the median nerve. He immediately loses sensation over the thumb, index, middle, and radial half of the ring finger (median nerve territory), and cannot flex these fingers or oppose his thumb. Surgical repair of the nerve is performed. Over the following weeks, the motor neurons in the spinal cord whose axons were severed undergo characteristic changes visible histologically: the Nissl bodies (aggregates of rough endoplasmic reticulum) appear to dissolve and disperse (chromatolysis), the nucleus moves from its central position to the cell periphery, and the cell body swells. This response represents the neuron shifting its metabolic priority from synaptic transmission to axon regeneration - upregulating proteins needed for axon regrowth while downregulating neurotransmitter synthesis. Because this is a peripheral nerve injury (PNS), regeneration is possible: Schwann cells proliferate and form bands of Bungner within their basal lamina tubes, guiding the regenerating axons. He gradually recovers motor and sensory function over 12-18 months. ### Key Learning Points - Nissl bodies represent aggregates of rough ER and ribosomes, responsible for the intense protein synthesis neurons require - Chromatolysis (dispersal of Nissl bodies, peripheral nuclear displacement, cell swelling) is the neuronal response to axon injury - The response reflects metabolic reprogramming: shifting from maintaining steady-state function to producing proteins for regeneration - Peripheral nerves can regenerate because Schwann cells and their basal lamina provide guidance channels for regrowing axons - Understanding the distribution of Nissl substance (present in soma and dendrites, absent from axon hillock and axon) helps explain why the cell body must provide all proteins for the axon --- ## Summary: Neuronal Disorders These cases illustrate how understanding neuronal structure informs clinical diagnosis: | Disorder | Structure Affected | Histological Finding | Clinical Correlation | |----------|-------------------|---------------------|---------------------| | **Alzheimer Disease** | Microtubules/tau protein | Neurofibrillary tangles (hyperphosphorylated tau) | Axonal transport disruption, neuronal death, dementia | | **Rabies** | Retrograde axonal transport | Negri bodies (viral inclusions in cytoplasm) | Virus travels from bite site to CNS via axonal transport | | **Peripheral Nerve Injury** | Nissl bodies (protein synthesis) | Chromatolysis (Nissl dissolution, nuclear displacement) | Metabolic shift to regeneration; PNS can regenerate | Knowledge of neuronal ultrastructure - Nissl bodies for protein synthesis, microtubules for transport, axon hillock as action potential initiation site - provides the foundation for understanding neurological disease.